Compositions and kits useful for treatment of respiratory illness

ABSTRACT

A stable liquid composition in a clear bottle where the composition contains, at least, phenylephrine and acetaminophen. The composition is substantially free of aldehydes and has a pH from 3.5 to 5. The clear bottle is a polyethylene terphthalate bottle.

FIELD OF THE INVENTION

The invention relates to a clear device: comprising a compositioncontained in a device; wherein said composition comprising apharmaceutical active selected from the group consisting ofphenylephrine, its free and addition salt forms, and mixtures thereof.

BACKGROUND OF THE INVENTION

The ability to produce a stable composition can be affected by the typeof container or device in which the composition is located. Thecontainer can be made of materials that have certain affinities foringredients contained within the composition for example pharmaceuticalactives such phenylephrine, acetaminophen and/ or dextromethorphan. Theinteraction, between the material that the container or device is madeof and ingredients comprised within the composition, can result inprecipitation of the ingredients and prevent appropriate dissolution ofthe ingredients within the composition.

Because these actives have different properties and stabilities, it is achallenge to formulate overall compositions containing actives whereinthe actives are all stable and effective in a device for delivering thecompositions and at the same time controlling the levels of ingredientsin the composition so as to prevent adverse side effects such asdiarrhea.

Therefore, the present invention provides suitable ranges of solventconcentrations and ratios that prevent the precipitation of actives,reduce aldehyde levels, and form stable compositions that deliveractives to a consumer in need all within a preferred device.

SUMMARY OF THE INVENTION

A stable liquid composition in a clear bottle comprising: (a) from about0.01% to about 0.25%, by weight the composition, phenylephrinehydrochloride wherein the phenylephrine hydrochloride is stable; (b) aflavor; (c) from about 40% to about 95% of total solvent, by weight ofthe composition, wherein the solvent is selected from the groupconsisting of water, propylene glycol, ethanol, glycerol, sorbitol, andmixtures thereof; (d) from greater than 0% to about 30% of total sugaror sweetener, by weight of the composition, wherein the sugar orsweetener is selected from the group consisting of glycerin, sorbitol,maltitol, mannitol, sodium saccharine, acesulfame potassium, sucralose,aspartame, monoammonium glycyrrhizinate, neohesperidin dihydrochalcone,thaumatin, neotame, cyclamates; (e) from about 0.01% to about 5%, byweight of the composition, acetaminophen; wherein said composition has apH of from about 3.5 to about 5; wherein said composition issubstantially free of aldehydes; wherein the clear bottle comprisespolyethylene terphthalate.

A stable liquid composition in a clear bottle comprising liquid doseswherein each dose comprises: (a) about 5 mg or 10 mg phenylephrinehydrochloride wherein the phenylephrine hydrochloride is stable; (b)from about 5 mg to about 650 mg acetaminophen; (c) from about 5 mg toabout 650 mg dextromethorphan; (d) a flavor; (e) from about 40% to about95% of total solvent, by weight of the composition, wherein the solventis selected from the group consisting of water, propylene glycol,ethanol, glycerol, sorbitol, and mixtures thereof; (f) from greater than0% to about 30% of total sugar or sweetener, by weight of thecomposition, wherein the sugar or sweetener is selected from the groupconsisting of glycerin, sorbitol, maltitol, mannitol, sodium saccharine,acesulfame potassium, sucralose, aspartame, monoammoniumglycyrrhizinate, neohesperidin dihydrochalcone, thaumatin, neotame,cyclamates; wherein the dose of the composition comprises from about 5mL to about 50 mL of the liquid composition; wherein said compositionhas a pH of from about 3.5 to about 5;—wherein said composition issubstantially free of aldehydes; wherein the clear bottle comprisespolyethylene terphthalate.

DETAILED DESCRIPTION OF THE INVENTION

The present invention comprises a clear device: comprising a compositioncontained in a device; wherein said composition comprising apharmaceutical active selected from the group consisting ofphenylephrine, its free and addition salt forms, and mixtures thereof;and wherein said device comprises a material selected from the groupconsisting of Polyethylene Terephthalate (PET), Glycol-modifiedPolyethylene Terephthalate (PETG), Oriented Polypropylene (OPP),Polyvinylchloride (PVC), Polyvinylidene Chloride (PVDC), Nylon,Polyethylene Terphthalate Polyester (PETP), Polyphene, and combinationsthereof.

These and other limitations of the compositions and methods of thepresent invention, as well as many of the optional ingredients suitablefor use herein, are described in detail hereinafter.

All weights, measurements and concentrations herein are measured at 25°C. on the composition in its entirety, unless otherwise specified.

All percentages, parts and ratios as used herein are by weight of thetotal composition, unless otherwise specified. All such weights as theypertain to listed ingredients are based on the active level and,therefore do not include solvents or by-products that may be included incommercially available materials, unless otherwise specified.

The composition and methods of the present invention can comprise,consist of, or consist essentially of, the essential elements andlimitations of the invention described herein, as well as any additionalor optional ingredients, components, or limitations described herein orotherwise useful in compositions intended for companion animalconsumption.

Device

The device of present invention preferably contains a composition.Nonlimiting examples of the device of the present invention include abottle, a canister, a container, and combinations. Preferably, thedevice is clear. Clear devices can include both colorless and coloredwhich permits the user to see the composition through the device. Thedevice comprises a material. Nonlimiting examples of a material that canbe used in the present invention include Polyethylene Terephthalate(PET), Glycol-modified Polyethylene Terephthalate (PETG), OrientedPolypropylene (OPP), Polyvinylchloride (PVC), Polyvinylidene Chloride(PVDC), Nylon, Polyethylene Terphthalate Polyester (PETP), Polyphene,and combinations thereof. Preferably the material of the presentinvention is PET.

Composition

The device of the present invention preferably contains a composition.The compositions of the present invention are made stable when placed indevices made of the material described herein. The compositions of thepresent invention comprise phenylephrine; phenylephrine free forms andaddition salt forms, and mixtures thereof. Nonlimiting salts ofphenylephrine include phenylephrine hydrochloride and phenylephrinehydrobromide.

The compositions of the present invention may comprise an amount ofphenylephrine in the range of about 0.0001 mg to about 60 mg ofphenylephrine, from about 0.01 to about 30 mg, from about 0.01 to about20 mg and from about 5 mg to about 10 mg of phenylephrine, all per doseof the composition. By way of non-limiting example, an embodiment of thepresent invention may comprise about 10 mg of phenylephrine, per dose.Another embodiment of the present invention may comprise about 5 mg ofphenylephrine, per dose.

The compositions of the present invention may comprise an amount ofphenylephrine in the range of from about 0.0001% to about 2%, from about0.0001% to about 1%, from about 0.001% to about 0.5%, and alternativelyfrom about 0.01% to about 0.25%, all by weight of the composition.

The compositions of the present invention may achieve enhanced stabilitywhen the composition has a pH of from about 2 to about 6.5, from about 2to about 5, from about 3.5 to about 5, and from about 4 to about 5. Asnon-limiting examples, the present compositions may comprise one or moreacidulants in order to reach, and maintain, the pH. Acidity can beadjusted to and maintained within the requisite range by known andconventional methods. Acidulant as used herein means a substance addedto a composition to lower the pH of the composition.

Organic as well as inorganic edible acids may be used to adjust the pHof the compositions herein. The acids can be present in theirundissociated form or, alternatively, as their respective salts, forexample, potassium or sodium hydrogen phosphate, potassium or sodiumdihydrogen phosphate salts. Illustrative acids are edible organic acidswhich include citric acid, malic acid, fumaric acid, adipic acid,phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, aceticacid, or mixtures thereof.

The compositions of the present invention are preferably substantiallyfree of aldehydes. As used herein, substantially free of aldehydes meansthat the composition comprises less than about 0.1%, alternatively lessthan about 0.05%, alternatively less than about 0.01% of totalaldehydes, (i.e. compounds containing at least one aldehydic moiety),all by weight of the composition. As the inventors have discovered,formulating the compositions of the present invention to besubstantially free of aldehydes upon manufacture compensates for thepotential for formation of some amount of aldehyde in the compositionduring storage conditions.

Aldehydes are compounds that are well known to the ordinarily skilledartisan. Flavors are well known for use in health products for improvingconsumer acceptance, and many such flavors are aldehydic in structure.For example, characterizing compounds for cherry flavors includebenzaldehyde and p-tolyl aldehyde. However, the inventors have foundthat these same flavors also often cause degradation of thephenylephrine used herein.

The present inventors have found that substantial removal of thealdehydes, as defined herein, greatly stabilizes the resultingcomposition.

Additional Pharmaceutical Actives

The compositions of the present invention can also comprise at least oneadditional pharmaceutical active. Pharmaceutical actives are readilyknown to the ordinarily skilled artisan and, as such, the actives arenot bound by the descriptions provided herein. Nonlimiting examples ofadditional pharmaceutical actives may include, but are not limited to,antitussives, antihistamines, non-sedating antihistamines,decongestants, expectorants, analgesics, antipyretic anti-inflammatoryagents, local anesthetics, anti-inflammatory agents, demulcents, herbalremedies, vitamins, supplements, antioxidants, natural ingredients,minerals, energy boosting ingredients, sleep aids and immune systemboosting ingredients, and mixtures thereof.

Nonlimiting examples of additional pharmaceutical actives include butare not limited to dextromethorphan, acetaminophen, ephedrine,pseudoephedrine, phenylpropanolamine, ibuprofen, aspirin, ketoprofen,guaifenesin, ambroxyl, bromhexine, diphenhydramine, chlorpheniramine,doxylamine, triprolidine, clemastine, pyrilamine, promethazine,cetirizine, loratidine, oxycodone, hydrocodone, naproxen,brompheniramine, carbinoxamine, caffeine, benzonatate, pheniramine,fentanyl, azatedine, desloratadine, carbamazepine, buprenorphine,hydromorphone, indomethacin, oxymorphone, phenol, codeine, mesalamine,dichlophenac, sulindac, beclomethaxone, meloxicam, fenoproten,mometasone, menthol, benzocaine, dipyridamole, methscopolamine, the freeand the addition salt forms, chamomile, passion flower, Vitamin C,Vitamin D, B Vitamins, echinacea, melatonin, green tea, curcumin, zinc,selenium, calcium, guarana, probiotics and mixtures thereof.

Preferably the additional pharmaceutical actives include but are notlimited to dextromethorphan, acetaminophen, doxylamine, and guaifenesin.

The compositions of the present invention may comprise an amount of atleast one additional pharmaceutical active in the range of about zero(0) mg to about 1,000 mg of each of at least one additionalpharmaceutical active, alternatively from about 2.5 mg to about 750 mg,and alternatively from about 5 mg to about 650 mg of each of at leastone additional pharmaceutical active, all per dose of the composition.

The compositions of the present invention may comprise an amount ofadditional pharmaceutical active in the range of about 0% to about 15%,alternatively 0.0001% to about 10%, alternatively from about 0.001% toabout 7%, and alternatively from about 0.01% to about 5%, all by weightof the composition.

Sweeteners

The composition of the present invention may comprise a sweetener toprovide sweetness and aid in the taste masking of a pharmaceuticalactive(s) as well as to provide some body and thickness. When asweetener is present in the present inventive composition, thecompositions may comprise from about 0.0001% to about 30% sweetener,from about 0.0001% to about 20% sweetener, alternatively from about fromabout 0.0001% to about 10% sweetener, alternatively from about fromabout 0.0001% to about 2% sweetener and alternatively from about 0.05%to about 1.0% sweetener, all by weight of the composition. Thesweeteners of the present invention can be artificial sweeteners and/ornatural sweeteners.

Non-limiting examples of artificial sweeteners are selected from thegroup consisting of sodium saccharine, acesulfame potassium, sucralose,aspartame, monoammonium glycyrrhizinate, neohesperidin dihydrochalcone,thaumatin, neotame, cyclamates, and mixtures thereof. Generally, suchartificial sweeteners are solids when used in sweetening compositionssuch as those of the present invention.

When an artificial sweetener is present in the present inventivecomposition, the compositions may comprise from about 0.0001% to about5% artificial sweetener, from about 0.0001% to about 3.5% artificialsweetener, alternatively from about from about 0.0001% to about 2.0%artificial sweetener, alternatively from about from about 0.0001% toabout 1.0% artificial sweetener and alternatively from about 0.05% toabout 1.0% artificial sweetener, all by weight of the composition.

Nonlimiting examples of natural sweeteners include sucrose, fructose,glucose, glycerin, sorbitol, maltitol, and mannitol and combinationsthereof. Sucrose, or table sugar, often in liquid form, may be used.However, sucrose can hydrolyze to its constituent sugars, namely glucoseand fructose. Glucose is an aldehyde, and therefore may be lessdesirable for use herein. However, the present inventors discover hereinthat the effect of a sweetener on phenylephrine is less than that oftraditional aldehyde-containing flavors and aromas. Nonetheless,improved stability can be achieved when low levels of sweeteners areused, in addition to inclusion of a non-aldehydic aesthetic agent if anaesthetic agent is used, such that the composition remains substantiallyfree of aldehydes as described herein. Relatively highly pure grades ofsweeteners, having undergone less hydrolysis to monosaccharides, mayassist in lowering levels of aldehydes as well. High fructose corn syrupcan also be used, though is less desirable because it containsaldehydes.

The compositions of the present invention can contain naturalsweeteners, such as sucrose. If the natural sweeteners are present in aliquid solution, then the natural sweeteners are present in the range offrom about 5% to about 30% by weight of the natural sweeteners solution,and alternatively from about 10% to about 25% by weight of the naturalsweeteners solution, wherein the natural sweeteners solution cancomprise from about 15% to about 20% by weight of the natural sweetenerssolution. If the natural sweeteners are present but not in a liquidsolution, then the natural sweeteners are present in the range of fromabout 4% to about 20% by weight composition, and alternatively fromabout 8% to about 17% by weight of the composition, wherein the naturalsweeteners solution can comprise from about 10% to about 13% by weightof the composition.

Additional Ingredients

Any or all components typically associated with respiratory illness andsymptom treatment products can be used as required or as additionalingredients herein. Nonlimiting examples of additional ingredientsinclude solvents, reducing agents, chloride salt, non-aldehydicaesthetic agent, coolant, colorant, preservative, fragrance, andcombinations thereof.

Solvents

The composition of the present invention can comprise a solvent. In oneembodiment, the solvent is water-soluble or water miscible. As usedherein, solvent means a substance used to dissolve phenylephrine and/orother pharmaceutical active(s). Non-limiting examples of solvents may beselected from water, propylene glycol, ethanol, glycerol, sorbitol, andmixtures thereof.

In one embodiment, the solvent is selected from water, propylene glycol,ethanol, polyethylene glycol (PEG) and mixtures thereof. There are alsomixtures of the solvents that may be useful for certain product forms ofthe present invention. For example, wherein the product form is anelixir, liquid-filled capsule or liquid-filled lozenge, the solvent mayoptionally be a mixture of propylene glycol, ethanol, and water.Additionally, for example, when the product form is a liquid filledcapsule, or liquid filled lozenge the solvent may optionally be PEG andwater.

The level of each solvent that makes up the mixture is dependent on thesolubility of the active(s) and the aesthetic benefits sought by theformulator. For example, for the compositions of the present invention,the composition may optionally comprise from about 40% to about 95%total solvents, or from about 50% to about 90%, or from about 60% toabout 85% total solvents, all by weight of the composition.

Chelating Agent

The present compositions may optionally comprise a chelating agent. Ithas been found that trace amounts of heavy metal ions may catalyzeauto-oxidation reactions that may compromise stability of the finalcomposition.

The compositions may therefore optionally include a chelating agent.Chelating agents are well known to the ordinarily skilled artisan.Non-limiting examples of chelating agents include but are not limited tothe salts of disodium and calcium salts of ethylene diamine tetraaceticacid (EDTA), tetrasodium EDTA, sodium hexametaphosphate (SHMP), citricacid, phosporic acid, di(hydroxyethyl)glycine, 8-hydroxyquinoline, andmixtures thereof. Trivalent metal chelating agents such asgalactomannans complexed with iron may also be useful.

Wherein the compositions herein comprise a chelaing agent, thecompositions may optionally comprise from about 0.0001% to about 1% ofthe chelating agent, alternatively from about 0.001% to about 0.5%, andalternatively from about 0.01% to about 0.3% of the chelating agent, allby weight of the composition.

Reducing Agents

The present compositions may also optionally comprise a reducing agent.The inclusion of a reducing agent may have a beneficial chemicalstabilizing effect on the pharmaceutical actives used in the presentinvention. Therefore, the reducing agents useful in the compositiondepend on the active selected and its solubility.

As used herein, the reducing agent is a substance that has a lower redoxpotential than the pharmaceutical active or other adjuvant that it isintended to protect from oxidation. Thus, reducing agents are morereadily oxidized than the pharmaceutical active or other adjuvant andare effective in the presence of oxidizing agents.

Reducing agents have an “electrode potential value”. The electrodepotential value is defined by the Nernst equation and measured usingstandard electrochemical reference cells. The resulting values aretherefore called the “Standard Electrode Potential”, or E⁰, as measuredin volts (V). Comparing Standard Electrode Potentials for differentsubstances can be used to assess the effectiveness of different reducingagents.

The reducing agents useful in the present invention may optionally haveE⁰ values greater than about −0.119V, and alternatively from about−0.119V to +0.250V. Illustrative reducing agents are selected from thesalts of metabisulfite and bisulfite, including their sodium andpotassium salts, dithiothreitol, thiourea, sodium thiosulphate,thioglycolic acid, tert-butyl hydroquinone (TBHQ), acetyl cysteine,hydroquinone, salts thereof, and mixtures thereof.

Wherein a reducing agent is utilized, the present compositions maycomprise from about 0.001% to 1%, alternatively from about 0.01% toabout 0.5%, and alternatively from about 0.05% to about 0.1% of areducing agent, all by weight of the composition.

Salts

The present compositions may optionally comprise a salt, such as achloride salt, which has been further discovered to provide potentialstability benefits. Non-limiting examples include sodium chloride,potassium chloride, ammonium chloride, and mixtures thereof.

Wherein the composition comprises a salt, the composition may optionallycomprise from about 0.0001% to about 2%, alternatively from about 0.25%to about 1% of the salt, all by weight of the composition. Such saltsmay slow the dissociation of a pharmaceutical active from thehydrochloride salt of a pharmaceutical active. For example, having achloride salt present slows the dissociation of phenylephrine fromphenylephrine hydrochloride.

Non-Aldehydic Aesthetic Agent

The present compositions may also optionally comprise a non-aldehydicaesthetic agent. Given the desire to provide compositions that areaesthetically acceptable, the present invention further providesoptional alternatives to typical flavors and aromas containingsignificant levels of aldehyde. Such alternatives are herein referencedas non-aldehydic aesthetic agents.

The inventors have discovered that typical flavors and aromas may besubstituted with non-aldehydic aesthetic agents such as flavorcomponents which are selected from the group consisting of esters,ketones and alcohols, and also sweeteners, and mixtures thereof, inorder to formulate flavors that smell and taste like cherry or otherdesired flavors.

As further examples, the present compositions may comprise anon-aldehydic aesthetic agent such as an ester selected from the groupconsisting of ethyl butyrate, benzyl acetate, benzyl butyrate, allylisovalerate, allyl caproate, ethyl-2-methyl butyrate, ethyl methylphenyl glycidate, and mixtures thereof. The compositions of the presentinvention may optionally contain from about 0.0001% to about 5%,alternatively from about 0.01% to about 2%, and alternatively from about0.025% to about 1.5% of non-aldehydic aesthetic agents, all by weight ofthe composition. Utilizing these fruity esters can readily generateflavors similar to cherry and berry flavors. The body of the flavor mayalso be important to make it take on character and endure. The use ofketones such as ionones are useful for this purpose. To illustrate,oxanone (4-(p-hydroxyphenyl)-2-butanone, raspberry ketone) along withtrace amounts of ionones can provide this body.

As a further example, compounds such as cis-3-hexenol andtrans-2-hexenyl acetate may add to the flavor. Furaneol and maltol mayadd a candy-like nuance. In addition, the compositions of the presentinvention may optionally comprise low-aldehyde juice concentrates asflavoring agents.

Methods of the Present Invention

In a further embodiment, the present invention is directed to methods oftreating a respiratory illness comprising orally administering acomposition as described herein to a mammal in need of such treatment.As used herein, the term “respiratory illness” encompasses a broad rangeof respiratory ailments, including viral infections such as influenzaand common cold, as well as allergy, sinusitis, rhinitis, and the like.As further used herein, “treatment” with respect to respiratory illnessmeans that administration of the referenced composition prevents,alleviates, ameliorates, inhibits, or mitigates one or more symptoms ofthe respiratory illness or the respiratory illness itself, or any likebenefit with respect to the respiratory illness in a mammalian subjectin need thereof, preferably in humans.

The present invention can also be directed to methods of preventionincluding preventing a respiratory illness or its associated symptomsfrom occurring in a mammal, for example when the mammal is predisposedto acquiring the respiratory illness, but has not yet been diagnosedwith the illness; inhibiting the respiratory illness or its associatedsymptoms; and/or alleviating, reversing, or curing the respiratoryillness or its associated symptoms. Insofar as the methods of thepresent invention are directed to preventing a respiratory illness, itis understood that the term “prevent” does not require that therespiratory illness be completely thwarted. Rather, as used herein, theterm “preventing” or the like refers to the ability of the skilledartisan to identify susceptibility to respiratory illness (such as, forexample, in humans during winter months), such that administration ofthe referenced compositions may occur prior to the onset of the symptomsassociated with the illness.

The present invention can also be directed to methods of recoveryincluding compositions that boost the energy of the mammal and boost theimmune system.

Respiratory illness may present as any of a variety of symptoms, such asrunny nose, nasal or chest congestion, cough, sneezing, pressure,headache, aches, fever, or sore throat. The mammal treated may be ahuman.

As used herein, the term “orally administering” with respect to themammal means that the mammal ingests or is directed to ingest, or doesingest, one or more of the present compositions. Wherein the human isdirected to ingest the composition, such direction may be that whichinstructs and/or informs the human that use of the composition mayand/or will provide the relief from the respiratory illness (e.g.symptomatic relief, whether temporary or permanent) for example, relieffrom congestion. For example, such direction may be oral direction(e.g., through oral instruction from, or example, a physician,pharmacists, or other heath professional), radio or television media(i.e., advertisement), or written direction (e.g., through writtendirection from, for example a physician, pharmacist, or other healthprofessional (e.g., scripts), sales professional or organization (e.g.,through, for example, marketing brochures, pamphlets, or otherinstructive paraphernalia), written media (e.g., internet, electronicmail, or other computer-related media), and/or packaging associated withthe composition (e.g., a label present on a container holding thecomposition). As used herein, “written” means through words, pictures,symbols, and/or other visible or tactile descriptors, such as Braille.Such information need not utilize the actual words used herein, forexample, “respiratory”, “illness”, or “mammal”, but rather use of words,pictures, symbols and the like conveying the same or similar meaning arecontemplated within the scope of this invention.

Administration may be on an as-needed or as-desired basis, for example,once-monthly, once-weekly, or daily, including multiple times daily, forexample, at least once daily, twice daily, three times daily, or fourtimes daily or more.

The amount of composition administered may be dependent on a variety offactors, including the general quality of health of the mammal, type ofmammal, age, gender, or severity of symptoms.

In one embodiment herein, the device delivers composition that isadministered to the mammal in total dosage volumes, per dose, of fromabout 5 mL to about 50 mL of the composition, alternatively of fromabout 10 mL to about 30 mL of the composition.

Kit

The present invention can also comprise a kit. The kit of the presentinvention can comprise: a composition contained in a device; whereinsaid composition comprising a pharmaceutical active selected from thegroup consisting of phenylephrine, its free and addition salt forms, andmixtures thereof; and wherein said device comprises amaterial selectedfrom the group consisting of Polyethylene Terephthalate (PET),Glycol-modified Polyethylene Terephthalate (PETG), OrientedPolypropylene (OPP), Polyvinylchloride (PVC), Polyvinylidene Chloride(PVDC), Nylon, Polyethylene Terphthalate Polyester (PETP), Polyphene,and combinations thereof.

The kit may further comprise at least one additional pharmaceuticalactive. The kit may also comprise an additional composition of thepresent invention in a full size, a sample size or both. The kit mayfurther comprise an additional composition that coordinates with thecomposition that is comprised within the device or attached to theoutside of the device. For, example if the composition contained in thedevice is a composition for the relief from congestion, the coordinatingcomposition may be for a headache. As well, if the composition in thedevice is a composition for runny nose, nasal or chest congestion,cough, sneezing, pressure, headache, aches, fever, or sore throat, thecoordinating composition may be a vitamin. The kit may further comprisea coupon, rebate, or advertisement. The kit may further comprise a setof instructions. These instructions may also include illustrations.

EXAMPLES

The following examples further describe and demonstrate embodimentswithin the scope of the present invention. They are given for thepurpose of illustration and are not to be construed as limitations ofthe present invention.

Examples

Below are illustrated various non-limiting examples of compositions ofthe present invention.

% w/w % w/w Raw Materials Ex. 1 Ex. 2 Propylene Glycol 40 30 DoxylamineSuccinate 0.08 0.08 Dextromethorphan HBr 0.13 0.13 Acetaminophen 4.434.43 Alcohol 8.52 8.52 Anethole 0.01 0.01 (Flavoring Agent) Glycerin 1010 Green Shade 0.005 0.005 Sodium Citrate 0.17 0.17 anhydrous CitricAcid 0.36 0.36 (Anhydrous) Phenylephrine HCl 0.07 0.07 Sodium Saccharin0.07 0.07 Sucrose Sweetner 31.11 21.16 solution Disodium EDTA 0.05Sorbitol Liquid 70% 20 Beta Carotene Water to 100% QS QS pH 4.16 4.10Green Shade available from Sensient Pharmaceuticals Tech, St. Louis,Mo., USA

Examples 1 and 2 can be made by first, add propylene glycol, alcohol andglycerin to a clean vessel. The additional pharmaceutical active(s),including, for example, acetaminophen, dextromethorphan, and doxylamine,then flavor is added and stirred until dissolved. In a separate vessel,water is added to dissolve phenylephrine, color, buffering agents,sweeteners, and EDTA. The aqueous solution is added to the propyleneglycol solution. The resulting composition is mixed with sweetenersolution and additional water and the composition is mixed untilhomogeneous and then placed in a device comprising the material PET.

% w/w % w/w RAW MATERIAL Ex. 3 Ex. 4 Water QS QS SodiumCarboxymethylcellulose 0.10 0.089 Sucrose sweetener solution 17 17.825Phenylephrine HCl 0.07 0.06 Propylene Glycol 40 35.6 Sorbitol 20 17.8Glycerin 5 4.45 Dextromethorphan HBr 0.13 0.11 Alcohol 4.25 3.79 Coolant0.02 .01 Flavor 0.33 0.30 Sodium Benzoate 0.1 0.089 Citric Acid 0.140.12 Sodium Chloride 0.50 0.44 Sodium Saccharin 0.09 0.08 Coloring Agent0.003 0.026 pH 4.5 4.7

-   Coolant available from Takasago International Corp., Tokyo, Japan-   Flavor available from IFF, Dayton, N.J., USA-   Coloring Agent available from Sensient Pharmaceuticals Tech, St.    Louis, MO, USA

Examples 3 and 4 can be made by first, add propylene glycol, and alcoholto a clean vessel. The additional pharmaceutical active(s), including,for example, acetaminophen and dextromethorphan, then flavor is addedand stirred until dissolved. In a separate vessel, water is added todissolve phenylephrine, color, buffering agents, and sweeteners. Theaqueous solution is added to the propylene glycol solution. Theresulting composition is mixed with sucrose sweetener solution andadditional water and the composition is mixed until homogeneous and thenplaced in a device comprising the material PET.

Ex. 5 Ex.6 Raw Material wt/wt wt/wt PROPYLENE GLYCOL USP 23.0202 22.7066SORBITOL SOLUTION 13.1544 12.9752 GLYCERIN 8 8 Sucrose Sweetenersolution 0 5 DEXTROMETHORPHAN 0.0614 0.0606 HYDROBROMIDE, USPAcetaminophen, USP 1.9951 1.9679 PHENYLEPHRINE HYDROCHLORIDE 0.03190.0315 Di sodium EDTA 0.05 0.05 Coolants 0.03 0.03 SODIUM BENZOATE NF,FCC 0.1 0.1 CITRIC ACID USP ANHYDROUS 0.2208 0.2245 Sodium Citrate,Dihydrate, USP 0.2035 0.2065 SODIUM CHLORIDE USP 0.5 0.5 SACCHARINSODIUM USP 0.1 0.1 Sucralose 0.07 0.07 FD&C Yellow #6 0.067 0.067 SODIUMCMC TYPE 7HOF USP 0.33 0.33 Flavorant 0.234 0.234 Water QS QS pH 4.5 4.5

Examples 5 and 6 can be made by first, add propylene glycol, and waterto a clean vessel. The additional pharmaceutical active(s), including,for example, acetaminophen and/or dextromethorphan, then flavor is addedand stirred until dissolved. In a separate vessel, water is added tohydrate sodium CMC and dissolve phenylephrine, color, buffering agents,sweeteners, preservatives, sodium chloride and EDTA. The aqueoussolution is added to the propylene glycol solution. The resultingcomposition is mixed with sucrose sweetener solution, sorbitol, glycerinand additional water and the composition is mixed until homogeneous andthen placed in a device comprising the material PET.

The dimensions and values disclosed herein are not to be understood asbeing strictly limited to the exact numerical values recited. Instead,unless otherwise specified, each such dimension is intended to mean boththe recited value and a functionally equivalent range surrounding thatvalue. For example, a dimension disclosed as “40 mm” is intended to mean“about 40 mm.”

Every document cited herein, including any cross referenced or relatedpatent or application and any patent application or patent to which thisapplication claims priority or benefit thereof, is hereby incorporatedherein by reference in its entirety unless expressly excluded orotherwise limited. The citation of any document is not an admission thatit is prior art with respect to any invention disclosed or claimedherein or that it alone, or in any combination with any other referenceor references, teaches, suggests or discloses any such invention.Further, to the extent that any meaning or definition of a term in thisdocument conflicts with any meaning or definition of the same term in adocument incorporated by reference, the meaning or definition assignedto that term in this document shall govern.

While particular embodiments of the present invention have beenillustrated and described, it would be obvious to those skilled in theart that various other changes and modifications can be made withoutdeparting from the spirit and scope of the invention. It is thereforeintended to cover in the appended claims all such changes andmodifications that are within the scope of this invention.

What is claimed is:
 1. A stable liquid composition in a clear bottlecomprising: a. from about 0.01% to about 0.25%, by weight of thecomposition, phenylephrine hydrochloride wherein the phenylephrinehydrochloride is stable; b. a flavor; c. from about 40% to about 95% oftotal solvent, by weight of the composition, wherein the solvent isselected from the group consisting of water, propylene glycol, ethanol,glycerol, sorbitol, and mixtures thereof; d. from greater than 0% toabout 30% of total sugar or sweetener, by weight of the composition,wherein the sugar or sweetener is selected from the group consisting ofglycerin, sorbitol, maltitol, mannitol, sodium saccharine, acesulfamepotassium, sucralose, aspartame, monoammonium glycyrrhizinate,neohesperidin dihydrochalcone, thaumatin, neotame, cyclamates; e. fromabout 0.01% to about 5%, by weight of the composition, acetaminophen;wherein said composition has a pH of from about 3.5 to about 5; whereinsaid composition is substantially free of aldehydes; wherein saidcomposition is a solution; wherein the clear bottle comprisespolyethylene terephthalate; wherein said composition comprises a ratioof propylene glycol: sorbitol: glycerin of about 2.9:1.2:1.0.
 2. Thestable liquid composition of claim 1 wherein the composition does notcomprise polyethylene glycol.
 3. The stable liquid composition of claim1 which has a pH of from about 4 to about
 5. 4. The stable liquidcomposition of claim 1 wherein the flavor does not comprise cherryflavor or berry flavor.
 5. The stable liquid composition of claim 1wherein the composition further comprises dextromethorphan.
 6. Thestable liquid composition of claim 1 wherein the sweetener consists ofsucralose and sodium saccharine.
 7. The stable liquid composition ofclaim 1 wherein the composition further comprises citric acid.
 8. Thestable liquid composition of claim 1 wherein the composition furthercomprises sodium benzoate.
 9. The stable liquid composition of claim 1wherein the composition further comprises a salt selected from the groupconsisting of sodium chloride, potassium chloride, ammonium chloride,and mixtures thereof.
 10. The stable liquid composition of claim 1wherein the composition further comprises a color.
 11. The compositionof claim 1 further comprising from about 0.025% to about 5% anon-aldehydic aesthetic agent.